This project aims to integrate advances in the field of psychiatry (i.e. continuation/maintenance pharmacotherapy for chronic, recurrent disorders) with alcoholism treatment. Although alcoholism is for many a chronic, recurrent syndrome, most clinical trials of pharmacologic treatments are designed for determining acute efficacy only. The acute efficacy of opiate antagonist treatment of alcoholism has been supported in studies with two simIlar compounds, naltrexone and nalmefene, in double-blind, placebo- controlled, 12-week studies. Subjects who remain in, and benefit from, acute nalmefene treatment are logical candidates for long-term nalmefene treatment, given the extremely high risk of relapse in chronic alcoholism. We propose to admit 184 alcohol dependent patients to 12 weeks of open treatment with fixed daily doses of 80 mg oral nalmefene and weekly coping skills therapy. Projections based on data from our current study indicate 114 patients will meet study criteria for response. Responders to short term open treatment will be randomized to a one year double-blind, placebo-controlled maintenance study to test the safety and efficacy of long-term nalmefene treatment of chronic alcoholism. All study participants will receive individual coping skills cognitive-behavioral therapy in keeping with good clinical practice and in recognition of the psychosocial aspects of chronic alcoholism. Drinking data will be collected from multiple sources, and standardized ratings of functioning, medical and emotional health status, and health-care utilization, will be obtained in a repeated measures design, with a six month post-treatment follow-up. Non responders will be given appropriate treatment referrals and will be paid for completing follow-up interviews. This study will provide vital information about (l) the efficacy of long-term nalmefene treatment in patients who respond to acute treatment; (2) evidence for tolerance to therapeutic effects during long-term treatment; (3) quantification of the costs and benefits of long-term treatment, in terms of side effects, health-related quality of life issues, and health services utilization; (4) whether long-term treatment with opiate antagonists alters the course of chronic alcoholism post treatment; and (5) predictors of acute and long-term outcome for potential use by clinicians to improve the matching of patients with treatments and thereby improve alcoholism treatment outcome.